Dynamic Balancing of Excitation and Inhiition During Gamma Oscillations

伽玛振荡期间激励和抑制的动态平衡

• 批准号: 7545004
• 负责人: Bassam Victor Atallah
• 金额: $ 3.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545004
• 关键词: Address; Area; Attention; Cells; Characteristics; Computer information processing; Depth; Equilibrium; Fire - disasters; Frequencies; Goals; Hippocampus (Brain); In Vitro; Individual; Measures; Nature; Neurons; Numbers; Pattern; Play; Process; Public Health; Purpose; Range; Role; Sensory Process; Stimulus; Synapses; Testing; extracellular; in vivo; patch clamp; postsynaptic; prevent; sensory stimulus; therapy development; time interval

DESCRIPTION (provided by applicant): PURPOSE: This proposal addresses how a balance between excitation and inhibition is maintained in cortical circuits during gamma oscillations. Specifically, I will determine the relationship between excitatory and inhibitory synaptic currents during rapidly modulated gamma oscillations. This study is performed in the hippocampus both in vivo and in vitro, using intracellular and extracellular electrophysiological recordings. BACKGROUND: Gamma oscillations, the synchronous spiking of neurons at frequencies of 20-80Hz, are believed to play a crucial role in the processing of sensory information. In vivo recordings from cortical areas have shown that gamma oscillations are evoked by sensory stimuli. In fact, the frequency and amplitude of these oscillations are modulated by the nature of the stimulus and the locus of attention. These ongoing changes in the firing frequency and number of neurons participating in oscillations produce rapidly changing patterns of synaptic activity. Balanced changes in excitatory and inhibitory synaptic activity determine the computations performed by cortical neurons and are a critical characteristic of cortical network stability. It is not known, however, how cortical networks of neurons maintain a balance between excitation and inhibition during this rapidly modulated gamma oscillations. Aim 1: Determine the relationship between excitatory and inhibitory currents during the modulation of gamma oscillation amplitude. Using simultaneous field and whole cell patch-clamp recordings in the hippocampus both in vivo and in vitro, I will test the hypothesis (I) that: inhibitory currents dynamically balance excitatory currents during modulated gamma oscillation amplitude. Aim 2: Determine the mechanisms underlying the modulation of gamma oscillation frequency. Using simultaneous field and whole cell patch-clamp recordings in the hippocampus both in vivo and in vitro, I will test the hypothesis (II) that: fluctuations in the amplitude of inhibitory synaptic currents modulate oscillation frequency by regulating the interval between individual oscillation cycles. PUBLIC HEALTH RELAVANCE: By establishing how inhibitory circuits rapidly balance changes in excitation, this study will elucidate the mechanisms that enable the cortex to robustly operate over a broad range of excitatory stimuli. A deeper understanding of the factors that regulate cortical excitability may contribute to the development of therapies aimed at preventing epileptogensis in cortical areas.

描述（由申请人提供）：目的：本提案阐述了在伽马振荡期间如何在皮层回路中维持兴奋和抑制之间的平衡。具体来说，我将确定在快速调制的伽马振荡兴奋性和抑制性突触电流之间的关系。这项研究是在海马在体内和体外进行的，使用细胞内和细胞外的电生理记录。背景技术背景：伽马振荡，即神经元在20- 80 Hz频率下的同步尖峰，被认为在感觉信息的处理中起着至关重要的作用。来自皮层区域的活体记录表明，伽马振荡是由感觉刺激引起的。事实上，这些振荡的频率和幅度是由刺激的性质和注意力的轨迹调制的。参与振荡的神经元的放电频率和数量的这些持续变化产生了快速变化的突触活动模式。兴奋性和抑制性突触活动的平衡变化决定了皮层神经元执行的计算，并且是皮层网络稳定性的关键特征。然而，在这种快速调制的伽马振荡过程中，神经元的皮层网络如何保持兴奋和抑制之间的平衡还不清楚。目的1：确定兴奋性电流和抑制性电流在γ振荡幅度调制过程中的关系。本论文采用在体和离体海马的同步场和全细胞膜片钳记录技术，对以下假设（I）进行了验证： 在调制的伽马振荡幅度期间平衡激发电流。目的2：确定伽马振荡频率调制的机制。使用同时场和全细胞膜片钳记录在海马在体内和体外，我将测试的假设（II），即：抑制性突触电流的幅度波动调制振荡频率通过调节个体振荡周期之间的间隔。公共卫生关系：通过建立抑制回路如何快速平衡兴奋的变化，本研究将阐明使皮层能够在广泛的兴奋性刺激下稳健运行的机制。更深入地了解调节皮质兴奋性的因素可能有助于开发旨在预防皮质区癫痫发生的治疗方法。